Data on the brain arachidonic acid (AA) metabolism during normal aging are limited and discrepant. AA is released from membrane phospholipids by phospholipase A2 (PLA2) and then further metabolized to bioactive prostaglandins and thromboxanes by cyclooxygenases (COX) -1 and -2. We examined the PLA2/COX pathway in the hippocampus and cerebral cortex of 4, 12, 24 and 30 month old rats. We found an increased level of thromboxane B2 in the brains of 24 and 30 month-old rats compared to 4 month-old rats. This increase was accompanied by an upregulation of COX-1 mRNA levels in the hippocampus at 12, 24, and 30 months compared to the 4 month-old rats. In contrast, COX-2 mRNA expression was slightly decreased only at 30 months. The upregulation of COX-1, which is predominantly expressed in glia, may be associated with glial activation reported in aging. The protein and mRNA levels of the Ca2+-independent PLA2 (iPLA2) were decreased in the hippocampus of 24 months and 30 months rats compared to the 4 month-old, with no significant change in Ca2+-dependent PLA2 expression. Since iPLA2 is thought to selectively release docosahexaenoic acid (DHA) from membrane phospholipids, its downregulation might contribute to alter phospholipid homeostasis. These specific alterations in the AA cascade observed in the hippocampus, which is critical for memory, may contribute to functional deficits occurring with aging.